Atelectasis Formation: Role of Positive Pressure Breathing, Hyperoxia, and Hypobaria

Influence of Hyperoxia and Hypobaria on Atelectasis Occurrence and Mitigation of Atelectasis Formation

The primary aim of this project is to get further knowledge of the physiology of flight atelectasis and its prevention. We seek to: 1) assess whether low levels of positive pressure breathing can prevent atelectasis formation in humans during exposure to hyperoxia and +Gz-accelerations. 2) get further knowledge on the effects of hypobaria on regional ventilation and perfusion.

A secondary aim is to evaluate the effect of anti G-trouser inflation on ventilation and regional perfusion.

Study Overview

• Status: Unknown
• Conditions: Pulmonary Atelectasis
• Intervention / Treatment: Other: +Gz accelerations and positive pressure breathing

Detailed Description

The effect of positive pressure breathing on lung function is being studied, when applied during exposure to hyperoxia and +Gz-accelerations. Focus is on lung tissue compression, ventilation and regional perfusion. In addition, the influence of hypobaria on these parameters is assessed.

This study is conducted in accordance with the amended Declaration of Helsinki. The Ethics Committee Ile-de-France III (ref. 3274) and the French National Agency for Drug Safety ANSM have approved the protocol (ref. ID RCB 2015-A00485-44 and ANSM 151046B-32).

Primary aim, item 1: Experiments are conducted in a human centrifuge. The protocol mimics a routine peacetime flight in combat aircraft, and includes 1hr05 min at +1Gz followed by 10-min exposure to +1.4 to +3.5Gz . Subjects are exposed three times to this sequence, breathing at positive pressure levels of 0, 5 or 10 hPa. Two groups of sixteen healthy male non-smoking volunteers, wearing anti-G trousers, are studied and compared: group 1 breathes air, group 2 100% O2.

Primary aim, item 2: Experiments are conducted in a hypobaric chamber. Sixteen healthy male non-smoking volunteers are exposed to four conditions: 0 or 15,000 ft altitude, breathing air or 100%O2. Protocol duration is 1h15min. Positive breathing pressure can be applied depending on the results of the experiments of item 1.

Secondary aim: Experiments are conducted in a human centrifuge. Sixteen healthy male non-smoking volunteers are exposed to four conditions: uninflated or inflated anti-G trousers (175 hPa), +1 or +3.5 Gz for 3 min.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stephanie S Montmerle-Borgdorff, MD, PhD; Phone Number: +33(1)78651249; Email: stephanie.montmerle@intradef.gouv.fr
• Study Contact Backup: Name: Catherine Verret, MD, PhD; Phone Number: +33(1)78651115; Email: catherine.verret@intradef.gouv.fr

Study Locations

• France
  • Brétigny-sur-Orge, France, 91 223
    • Recruiting
    • Armed Forces Biomedical Research Institute
    • Contact: Stephanie S Montmerle-Borgdorff, MD, PhD; Phone Number: +33(1)78651249; Email: stephanie.montmerle@intradef.gouv.fr
    • Contact: Maquilon-Lefebvre David, nurse; Phone Number: +33(1)78651091; Email: david.maquilon@intradef.gouv.fr
    • Principal Investigator: Stephanie S Montmerle-Borgdorff, MD, PhD
    • Sub-Investigator: Göran Hedenstierna, Pr, MD, PhD
    • Sub-Investigator: João Batista Borges, MD, PhD
    • Sub-Investigator: Caroline Dussault, PhD
  • Clamart, France, 92140
    • Active, not recruiting
    • Department of Radiology, Percy hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• normal lung function checked by pulmonary function tests.
• normal ECG
• normal clinical examination

Aim 1 exclusion criteria:

• smoking
• myopia
• past medical history of heart or lung disease
• current medical treatment for heart or lung disease
• past medical history of back pain or spine trauma or disease
• otitis
• bad tolerance to +Gz accelerations (G-induced loss of consciousness, motion sickness)
• claustrophobia in the centrifuge gondola

Aim 2 exclusion criteria:

• smoking
• past medical history of heart or lung disease
• current medical treatment for heart or lung disease
• otitis
• bad tolerance to the altitude chamber (15,000 ft): ear pain, claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 100%O2 breathing; Primary aim, item 1	Other: +Gz accelerations and positive pressure breathing
Experimental: Air breathing; Primary aim, item 1	Other: +Gz accelerations and positive pressure breathing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
atelectasis formation (change between pre and post-protocol)	computerized tomography: 0-5 scale for size and localization	pre-protocol (baseline) and 1h30 min after centrifuge stop
change in pulmonary ventilation between 1 Gz, 1.6 Gz and 3.5 Gz	electrical impedance tomography: deltaZ on regions of interest	pre-protocol (baseline), baseline + 1hr, baseline +1h10 min, baseline +1h15 min
change in pulmonary tissue density from baseline at centrifuge stop and 1h30 min after stop	ultrasound: number of lung comets + localization	pre protocol (baseline), at centrifuge stop (baseline + 1h15 min) and 1h30 min after centrifuge stop

Collaborators and Investigators

• Sponsor: Direction Centrale du Service de Santé des Armées
• Collaborators: Uppsala University Hospital; Percy Hospital
• Investigators: Study Chair: Dominique Felten, MD, Armed Forces Biomedical Research Institute

Publications and helpful links

General Publications

• Dussault C, Gontier E, Verret C, Soret M, Boussuges A, Hedenstierna G, Montmerle-Borgdorff S. Hyperoxia and hypergravity are independent risk factors of atelectasis in healthy sitting humans: a pulmonary ultrasound and SPECT/CT study. J Appl Physiol (1985). 2016 Jul 1;121(1):66-77. doi: 10.1152/japplphysiol.00085.2016. Epub 2016 Apr 21.
• Borges JB, Hedenstierna G, Bergman JS, Amato MB, Avenel J, Montmerle-Borgdorff S. First-time imaging of effects of inspired oxygen concentration on regional lung volumes and breathing pattern during hypergravity. Eur J Appl Physiol. 2015 Feb;115(2):353-63. doi: 10.1007/s00421-014-3020-9. Epub 2014 Oct 17.

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2015
• Primary Completion (Anticipated): June 30, 2019
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: April 5, 2017
• First Submitted That Met QC Criteria: October 11, 2017
• First Posted (Actual): October 17, 2017

Study Record Updates

• Last Update Posted (Actual): May 14, 2019
• Last Update Submitted That Met QC Criteria: May 13, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: oxygen; computed tomography; electrical impedance tomography; pulmonary ultrasound; hypergravity; human physiology; lung ventilation; lung perfusion; altitude chamber
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Signs and Symptoms, Respiratory; Pulmonary Atelectasis; Hyperoxia
• Other Study ID Numbers: PDH1-SMO2-0714

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No